Accelerated linear growth, closure of the epiphyses and development of secondary sexual characteristics are major milestones of puberty. The specific factors that initiate and sustain these processes and their relationship to the maturation of adrenal androgen secretion are obscure. A major objective of the proposed research is to establish by longitudinal study, any distinct temporal relationship which might exist between gonadotropin and gonadal secretion on the one hand, and that of the adrenal androgens on the other. This will be done in individual normal children from pre- to post-puberty. Another objective is to define the role of the adrenal androgens in skeletal maturation during puberty, and to assess their role in the emergence of secondary sex characteristics in the normal female. To help in this aim, patients with various disorders of endocrine function affecting their growth and maturation will be studied longitudinally and the effects of appropriate hormonal therapy will be monitored. From these observations the factors that relate to the maturation of the adrenal at puberty and modulate its androgen secretion may be elucidated. In order to complement the in vivo studies, we will assess the influence of gonadal and adrenal androgens upon chick embryo hindleg rudiments in organ culture. The major aims will be to establish biochemical, histological and histochemical indicators of bone growth and maturation in culture to compare the activity of the sex steroids and adrenal androgens in this system and to assess the importance of hormonal metabolism by the bone rudiments for biologic action. Finally, we will attempt to identify the responsive cell type and the locus of action of these steroids which promote bone growth or maturation in culture.